The present invention is related to novel intermediates which are useful in the preparation of certain piperidine derivatives which are useful as antihistamines, antiallergy agents and bronchodilators [U.S. Pat. No. 4,254,129, Mar. 3, 1981, U.S. Pat. No. 4,254,130, Mar. 3, 1981, U.S. Pat. No. 4,285,958, Apr. 25, 1981 and U.S. Pat. No. 4,550,116, Oct. 29, 1985].
These antihistaminic piperidine derivatives can be described by the following formula: ##STR2##
wherein
W represents --C(.dbd.O)-- or --CH(OH)--; PA1 R.sub.1 represents hydrogen or hydroxy; PA1 R.sub.2 represents hydrogen; PA1 R.sub.1 and R.sub.2 taken together form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 ; PA1 n is an integer of from 1 to 5; PA1 m is an integer 0 or 1; PA1 R.sub.3 is --COOH or --COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; PA1 each of A is hydrogen or hydroxy; and PA1 pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R.sub.1 and R.sub.2 are taken together to form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 or where R.sub.1 represented hydroxy, m is an integer 0. PA1 W represents --C(.dbd.O)-- or --CH(OH)--; PA1 R.sub.1 represents hydrogen or hydroxy; PA1 R.sub.2 represents hydrogen; or PA1 R.sub.1 and R.sub.2 taken together form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 ; PA1 n is an integer of from 1 to 5; PA1 m is an integer 0 or 1; PA1 R.sub.3 is --COOH or --COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; PA1 each of A is hydrogen or hydroxy; and PA1 pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R.sub.1 and R.sub.2 are taken together to form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 or where R.sub.1 represented hydroxy, m is an integer 0. PA1 A is a hydrogen or hydroxy; and PA1 R.sub.5 is H, --CH.sub.2 OD wherein D is hydrogen, acetate or benzoate, --CHO, Br, Cl, I, CN, --COOH, --COOalkyl or --CONR.sub.6 R.sub.7 wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched and R.sub.6 and R.sub.7 are each independently H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or R.sub.6 and R.sub.7 taken together with the nitrogen atom form a pyrrolidine, piperidine or morpholine, with the proviso that R.sub.6 and R.sub.7 cannot both be represented by C.sub.1 -C.sub.6 alkoxy. ##STR5## PA1 A is a hydrogen or hydroxy; and PA1 R.sub.5 is H, Br, Cl, I, CN, --COOH, --COOalkyl or --CONR.sub.6 R.sub.7 wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched and R.sub.6 and R.sub.7 are each independently H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or R.sub.6 and R.sub.7 taken together with the nitrogen atom form a pyrrolidine, piperidine or morpholine, with the proviso that R.sub.6 and R.sub.7 cannot both be represented by C.sub.1 -C.sub.6 alkoxy. ##STR6## PA1 A is a hydrogen or hydroxy; and PA1 R.sub.5 is H, Br, Cl, I, CN, --COOH, --COOalkyl or --CONR.sub.6 R.sub.7 wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched and R.sub.6 and R.sub.7 are each independently H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or R.sub.6 and R.sub.7 taken together with the nitrogen atom form a pyrrolidine, piperidine or morpholine, with the proviso that R.sub.6 and R.sub.7 cannot both be represented by C.sub.1 -C.sub.6 alkoxy. ##STR7## PA1 Hal is Cl, Br or I; PA1 n is an integer of from 1 to 5; PA1 A is a hydrogen or hydroxy; and PA1 R.sub.5 is H, CH.sub.2 OD wherein D is hydrogen, acetate or benzoate, CHO, Br, Cl, I, CN, --COOH or --CONR.sub.6 R.sub.7 wherein R.sub.6 and R.sub.7 are each independently H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or R.sub.6 and R.sub.7 taken together with the nitrogen atom form a pyrrolidine, piperidine or morpholine, with the proviso that R.sub.6 and R.sub.7 cannot both be represented by C.sub.1 -C.sub.6 alkoxy. ##STR8## PA1 Hal is Cl, Br or I; PA1 n is an integer of from 1 to 5; PA1 A is a hydrogen or hydroxy; and PA1 R.sub.5 is H, Br, Cl, I, CN, --COOH, --COOalkyl or --CONR.sub.6 R.sub.7 wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched and R.sub.6 and R.sub.7 are each independently H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or R.sub.6 and R.sub.7 taken together with the nitrogen atom form a pyrrolidine, piperidine or morpholine, with the proviso that R.sub.6 and R.sub.7 cannot both be represented by C.sub.1 -C.sub.6 alkoxy. ##STR9## PA1 Hal is Cl, Br or I; PA1 n is an integer of from 1 to 5; PA1 A is a hydrogen or hydroxy; PA1 R.sub.5 is H, Br, Cl, I, CN, --COOH, --COOalkyl or --CONR.sub.6 R.sub.7 wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched and R.sub.6 and R.sub.7 are each independently H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or R.sub.6 and R.sub.7 taken together with the nitrogen atom form a pyrrolidine, piperidine or morpholine, with the proviso that R.sub.6 and R.sub.7 cannot both be represented by C.sub.1 -C.sub.6 alkoxy. ##STR10## PA1 Hal is Cl, Br or I; PA1 n is an integer of from 1 to 5; and PA1 A is a hydrogen or hydroxy. ##STR11## PA1 Hal is Cl, Br or I; PA1 n is an integer of from 1 to 5; PA1 A is a hydrogen or hydroxy; and PA1 R.sub.5 is H, CH.sub.2 OD wherein D is hydrogen, acetate or benzoate, CHO, Br, Cl, I, CN, --COOH, --COOalkyl or --CONR.sub.6 R.sub.7 wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched and R.sub.6 and R.sub.7 are each independently H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or R.sub.6 and R.sub.7 taken together with the nitrogen atom form a pyrrolidine, piperidine or morpholine, with the proviso that R.sub.6 and R.sub.7 cannot both be represented by C.sub.1 -C.sub.6 alkoxy; and PA1 individual optical isomers thereof. ##STR13## PA1 W represents --C(.dbd.O)-- or --CH(OH)--; PA1 R.sub.1 represents hydrogen or hydroxy; PA1 R.sub.2 represents hydrogen; or PA1 R.sub.1 and R.sub.2 taken together form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 ; PA1 n is an integer of from 1 to 5; PA1 m is an integer 0 or 1; PA1 R.sub.5 is H, Br, Cl, I, CN or --CONR.sub.6 R.sub.7 wherein R.sub.6 and R.sub.7 are each independently H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or R.sub.6 and R.sub.7 taken together with the nitrogen atom form a pyrrolidine, piperidine or morpholine, with the proviso that R.sub.6 and R.sub.7 cannot both be represented by C.sub.1 -C.sub.6 alkoxy; PA1 A is hydrogen or hydroxy; and PA1 pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R.sub.1 and R.sub.2 are taken together to form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 or where R.sub.1 represented hydroxy, m is an integer 0. PA1 W represents --C(.dbd.O)-- or --CH(OH)--; PA1 R.sub.1 represents hydrogen or hydroxy; PA1 R.sub.2 represents hydrogen; or PA1 R.sub.1 and R.sub.2 taken together form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 ; PA1 n is an integer of from 1 to 5; PA1 m is an integer 0 or 1; PA1 R.sub.3 is --COOH or --COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; PA1 each of A is hydrogen or hydroxy; and PA1 pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R.sub.1 and R.sub.2 are taken together to form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 or where R.sub.1 represented hydroxy, m is an integer 0, comprising the steps of: PA1 (a) reacting a cumene compound of the formula ##STR15## PA1 (b) reacting the .omega.-halo cumylketone compound with a suitable halogenating agent to give a .omega.-halo-halocumylketone compound; PA1 (c) reacting the .omega.-halo-halocumylketone compound compound with a suitable cyanating agent to give a .omega.-halo-cyanocumylketone compound; PA1 (d) reacting the .omega.-halo-cyanocumylketone compound with an appropriate straight or branched C.sub.1 -C.sub.6 alcohol in the presence of a suitable anhydrous acid to give a .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid imidate compound; PA1 (e) reacting the .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid imidate compound with water to give a .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid ester compound; PA1 (f) reacting the .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid ester compound with a piperidine compound of the formula ##STR17## PA1 (g) optionally hydrolyzing the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOalkyl and W is --C(.dbd.O)-- to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)--; PA1 (h) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOalkyl and W is --C(.dbd.O)-- or the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)-- with a suitable reducing agent to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)--; and PA1 (i) optionally reacting the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the appropriate .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)-- with an appropriate straight or branched C.sub.1 -C.sub.6 alcohol in the presence of a suitable acid to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- or a .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--; and PA1 (j) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- with an appropriate deprotecting reagent, PA1 W represents --C(.dbd.O)-- or --CH(OH)--; PA1 R.sub.1 represents hydrogen or hydroxy; PA1 R.sub.2 represents hydrogen; or PA1 R.sub.1 and R.sub.2 taken together form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 ; PA1 n is an integer of from 1 to 5; PA1 m is an integer 0 or 1; PA1 R.sub.3 is --COOH or --COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; PA1 each of A is hydrogen or hydroxy; and PA1 pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R.sub.1 and R.sub.2 are taken together to form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 or where R.sub.1 represented hydroxy, m is an integer 0, comprising the steps of: PA1 (a) reacting a .omega.-halo-halocumylketone compound with carbon dioxide under electrochemical reduction conditions to give a .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic compound; PA1 (b) reacting the .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic compound compound with an appropriate straight or branched C.sub.1 -C.sub.6 alcohol in the presence of a suitable anhydrous acid to give a .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid ester compound; PA1 (c) reacting the .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid ester compound with a piperidine compound of the formula wherein R.sub.1, R.sub.2 and m are as defined above in the presence of a suitable non-nucleophilic base to produce a .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOalkyl and W=--C(.dbd.O)--; PA1 (d) optionally hydrolyzing the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is ##STR19## PA1 COOalkyl and W is --C(.dbd.O)-- to produce a .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)--; PA1 (e) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOalkyl and W is --C(.dbd.O)-- or the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)-- with a suitable reducing agent to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)--; and PA1 (f) optionally reacting the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the appropriate .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)-- with an appropriate straight or branched C.sub.1 -C.sub.6 alcohol in the presence of a suitable acid to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- or a .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--; and PA1 (g) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- with an appropriate deprotecting reagent, PA1 W represents --C(.dbd.O)-- or --CH(OH)--; PA1 R.sub.1 represents hydrogen or hydroxy; PA1 R.sub.2 represents hydrogen; or PA1 R.sub.1 and R.sub.2 taken together form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 ; PA1 n is an integer 3; PA1 m is an integer 0 or 1; PA1 R.sub.3 is --COOH or --COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; PA1 each of A is hydrogen or hydroxy; and PA1 pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R.sub.1 and R.sub.2 are taken together to form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 or where R.sub.1 represented hydroxy, m is an integer 0, comprising the steps of: PA1 (a) reacting a cumyl compound of the formula ##STR21## PA1 (b) reacting the cyclopropyl cumylketone compound with a suitable halogenating agent to give a cyclopropyl halocumylketone compound; PA1 (c) reacting the cyclopropyl halocumylketone compound with carbon dioxide under electrochemical reduction conditions to give a cyclopropylketo-.alpha.,.alpha.-dimethylphenylacetic acid compound; PA1 (d) reacting the cyclopropylketo-.alpha.,.alpha.-dimethylphenylacetic with an appropriate straight or branched C.sub.1 -C.sub.6 alcohol in the presence of a suitable anhydrous acid to give a .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid ester compound; PA1 (e) reacting the .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid ester compound with a piperidine compound of the formula ##STR23## PA1 (f) optionally hydrolyzing the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOalkyl and W is --C(.dbd.O)-- to produce a .omega.'piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)--; PA1 (g) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOalkyl and W is --C(.dbd.O)-- or the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)-- with a suitable reducing agent to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)--; and PA1 (h) optionally reacting the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the appropriate .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)-- with an appropriate straight or branched C.sub.1 -C.sub.6 alcohol in the presence of a suitable acid to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- or a .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--; and PA1 (i) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- with an appropriate deprotecting reagent, PA1 W represents --C(.dbd.O)-- or --CH(OH)--; PA1 R.sub.1 represents hydrogen or hydroxy; PA1 R.sub.2 represents hydrogen; or PA1 R.sub.1 and R.sub.2 taken together form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 ; PA1 n is an integer of from 1 to 5; PA1 m is an integer 0 or 1; PA1 R.sub.3 is --COOH or --COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; PA1 each of A is hydrogen or hydroxy; and PA1 pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R.sub.1 and R.sub.2 are taken together to form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 or where R.sub.1 represented hydroxy, m is an integer 0, comprising the steps of: PA1 (a) reacting a .alpha.,.alpha.-dimethylphenylacetic acid amide compound of the formula ##STR25## PA1 (b) reacting the .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid amide compound with a piperidine compound of the formula ##STR27## PA1 (c) optionally hydrolyzing the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (XI) wherein R.sub.5 is --CONR.sub.6 R.sub.7 wherein R.sub.6 and R.sub.7 are as defined above to produce a .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)--; PA1 (d) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)-- with a suitable reducing agent to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)--; and PA1 (e) optionally reacting the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the appropriate .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)-- with an appropriate straight or branched C.sub.1 -C.sub.6 alcohol in the presence of a suitable acid to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- or a .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--; and PA1 (f) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- with an appropriate deprotecting reagent, PA1 W represents --C(.dbd.O)-- or --CH(OH)--; PA1 R.sub.1 represents hydrogen or hydroxy; PA1 R.sub.2 represents hydrogen; or PA1 R.sub.1 and R.sub.2 taken together form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 ; PA1 n is an integer of from 1 to 5; PA1 m is an integer 0 or 1; PA1 R.sub.3 is --COOH or --COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; PA1 each of A is hydrogen or hydroxy; and PA1 pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R.sub.1 and R.sub.2 are taken together to form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 or where R.sub.1 represented hydroxy, m is an integer 0, comprising the steps of: PA1 (a) reacting a toluene compound of the formula ##STR29## PA1 (b) reacting the .omega.-halo-tolylketone compound with a suitable base to give a cyclopropyl-tolylketone compound; PA1 (c) reacting the cyclopropyl-tolylketone compound with a suitable halogenating agent to give a cyclopropyl-halotolylketone compound; PA1 (d) reacting the cyclopropyl-halotolylketone compound with a suitable cyanating agent to give a cyclopropyl cyanotolylketone compound; PA1 (e) reacting the cyclopropyl cyanotolylketone compound with a suitable methylating agent to give a cyclopropyl cyanocumylketone compound; PA1 (f) reacting the cyclopropyl cyanocumylketone compound with a suitable base to give a cyclopropylketo-.alpha.,.alpha.-dimethylphenylacetic acid amide; PA1 (g) reacting the cyclopropylketo-.alpha.,.alpha.-dimethylphenylacetic acid amide with an appropriate straight or branched C.sub.1 -C.sub.6 alcohol in the presence of a suitable anhydrous acid to give a .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid ester compound; PA1 (h) reacting the .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid ester compound with a piperidine compound of the formula ##STR31## PA1 (i) optionally hydrolyzing the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative to produce a .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)--; PA1 (j) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)-- with a suitable reducing agent to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)--; and PA1 (k) optionally reacting the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the appropriate .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)-- with an appropriate straight or branched C.sub.1 -C.sub.6 alcohol in the presence of a suitable acid to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- or a .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (II) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--; and PA1 (l) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (II) wherein R.sub.3 is --COOH and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (II) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.dimethylphenyl of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- with an appropriate deprotecting reagent, PA1 W represents --C(.dbd.O)-- or --CH(OH)--; PA1 R.sub.1 represents hydrogen or hydroxy; PA1 R.sub.2 represents hydrogen; or PA1 R.sub.1 and R.sub.2 taken together form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 ; PA1 n is an integer of from 1 to 5; PA1 m is an integer 0 or 1; PA1 R.sub.3 is --COOH or --COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; PA1 each of A is hydrogen or hydroxy; and PA1 pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R.sub.1 and R.sub.2 are taken together to form a second bond between the carbon atoms bearing R.sub.1 and R.sub.2 or where R.sub.1 represented hydroxy, m is an integer 0, comprising the steps of: PA1 (a) reacting a phenylacetic acid ester compound of the formula ##STR33## PA1 (b) reacting the .omega.'-halo-.alpha.'-keto-phenylacetic acid ester compound with a suitable methylating agent in the presence of a suitable base to give a cyclopropylketo-.alpha.,.alpha.dimethylphenylacetic acid ester; PA1 (c) purifying the cyclopropylketo-.alpha.,.alpha.-dimethylphenylacetic acid ester by distillation and/or recrystallization; PA1 (d) reacting the cyclopropylketo-.alpha.,.alpha.-dimethylphenylacetic acid ester with an appropriate straight or branched C.sub.1 -C.sub.6 alcohol in the presence of a suitable anhydrous acid to give a .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid ester compound; PA1 (e) reacting the .omega.'-halo-.alpha.'-keto-.alpha.,.alpha.-dimethylphenylacetic acid ester compound with a piperidine compound of the formula ##STR35## PA1 (f) optionally hydrolyzing the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)-- to produce a .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)--; PA1 (g) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)-- with a suitable reducing agent to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)--; and PA1 (h) optionally reacting the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the appropriate .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)-- with an appropriate straight or branched C.sub.1 -C.sub.6 alcohol in the presence of a suitable acid to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- or a .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--; and PA1 (i) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- with an appropriate deprotecting reagent, PA1 (g) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is COOH and W is --C(.dbd.O)-- with a suitable reducing agent to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)--; and PA1 (h) optionally reacting the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the appropriate .omega.'-piperidine-.alpha.'-keto-60 ,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)-- with an appropriate straight or branched C.sub.1 -C.sub.6 alcohol in the presence of a suitable acid to produce a .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- or a .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--; and PA1 (i) optionally reacting the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-keto-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOalkyl and W is --C(.dbd.O)--, the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl derivative of formula (I) wherein R.sub.3 is --COOH and W is --CH(OH)-- or the .omega.'-piperidine-.alpha.'-hydroxy-.alpha.,.alpha.-dimethylphenyl of formula (I) wherein R.sub.3 is --COOalkyl and W is --CH(OH)-- with an appropriate deprotecting reagent, PA1 wherein B is as previously defined to give the corresponding cyclopropyl tolylketone derivative of structure (5) as described previously in step d. PA1 wherein B is as previously defined to give the corresponding cyclopropyl ethylphenylketone derivative of structure (7) as described previously in step e. PA1 wherein B is as previously defined to give the corresponding cyclopropyl cumylketone derivative of structure (9) as described previously in step e.